The general goal of the prospective studies is to understand the causes of the aging process in animals. Endogenously-generated oxygen free radicals have been widely postulated to play a causal role in the aging process; however, critical studies testing the validity of this hypothesis have not as yet been conducted. The purpose of the proposed experiments is to determine if oxidative stress is a causal factor in governing the rate of aging in Drosophila melanogaster, using a molecular genetic approach. The effect of overexpression of antioxidant genes for superoxide dismutase, catalase and seleno-dependent glutathione peroxidase, either alone or in combination, on life span and age-related changes in Drosophila will be examined. Because the overexpression on one antioxidant gene may create a biochemical imbalance in the inter-related defense mechanisms, a major effort will be made to construct transgenic strains with balanced antioxidant defenses. Results of this study should indicate if the primary enzymatic defense against partially reduced oxygen species are a causal factor in the aging process of Drosophila.